Alpha-branched alkenoic acids and the use of alpha-branched alkanoic and alkenoic acids as a fragrance

ABSTRACT

The present invention refers to alpha branched alkanoic and alkenoic acids of formula (I) 
     
       
         
         
             
             
         
       
         
         
           
             wherein X and R have the same meaning as given in the description. The invention further refers to perfume compositions and fragrance applications comprising them.

The present application is a continuation of co-pending U.S. Ser. No.13/130,847, having a 371(c) date of May 24, 2011, which is a nationalstage application of International Application No. PCT/CH2009/000385,filed Dec. 2, 2009, which claims priority from Great Britain PatentApplication Serial No. 0822091.5, filed Dec. 3, 2008, and which areincorporated herein by reference.

The present invention refers to alpha branched alkanoic and alkenoicacids and their use as odorants. This invention relates furthermore to amethod of their production and fragrance compositions comprising them.

In the fragrance industry there is a constant demand for new compoundsthat enhance, modify or improve on odour notes. Surprisingly, it has nowbeen found that alpha branched alkanoic and alkenoic acids of formula(I) as defined below constitute very powerful olibanum, citrus odorantswhereas the corresponding carboxylic acids without the substituent X aredescribed possessing a fatty, waxy, sour and acidic odour note.

Accordingly, the present invention refers in one of its aspects to theuse as fragrance of a compound of formula (I)

wherein

X is selected from methyl and ethyl;

R is selected from C₄-C₆ alkyl (e.g. pentyl), and C₄-C₆ alkenyl (e.g.but-2-enyl, but-3-enyl, pentenyl such as pent-3-enyl, pent-4-enyl, andhex-4-enyl).

The compounds of formula (I) may comprise one or several chiral centresor E- or Z-configured double bonds and as such may exist as a mixture ofstereoisomers, or they may be resolved into isomerically pure forms.Resolving stereoisomers adds to the complexity of manufacture andpurification of these compounds and so it is preferred to use thecompounds as mixtures of their stereoisomers simply for economicreasons. However, if it is desired to prepare individual stereoisomers,this may be achieved according to methods known in the art, e.g.preparative HPLC and GC, crystallization or stereoselective synthesis.

Non-limiting examples are compound of formula (I) wherein X is methyland R is linear C₄-C₆ alkyl, and compounds of formula (I) wherein X isethyl and R is linear C₄-C₆ alkyl.

Further, non-limiting examples are compounds of formula (I) wherein X ismethyl and R is linear C₄-C₆ alkenyl, and compounds of formula (I)wherein X is ethyl and R is linear C₄-C₆ alkenyl.

In particular embodiments are compounds of formula (I) selected from thelist consisting of 2-methyl decanoic acid, 2-methyl undecanoic acid,2-ethyl decanoic acid, 2-ethyl undecanoic acid, 2-methyl undec-9-enoicacid, 2-methyl undec-10-enoic acid, 2-methyl undec-8-enoic acid,2-methyl undec-7-enoic acid and 2-methyl dodecanoic acid.

Amongst the compounds of formula (I), one may cite 2-methyl undecanoicacid, which is one of the most appreciated by the perfumer. Thiscompound possess a very powerful and diffusive note of aldehyde andnatural resins mainly olibnum and myrrh combined with a sparkling elemidimension and orris and ambrette seed background. This compound possessall the odor adtributes linked to a natural frankincense which howeverneeds burning for developing the typical fragrance note.

The compounds of formula (I) may be used alone, as mixtures thereof, orin combination with a base material. As used herein, the “base material”includes all known odorant molecules selected from the extensive rangeof natural products and synthetic molecules currently available, such asessential oils, alcohols, aldehydes and ketones, ethers and acetals,esters and lactones, macrocycles and heterocycles, and/or in admixturewith one or more ingredients or excipients conventionally used inconjunction with odorants in fragrance compositions, for example,carrier materials, and other auxiliary agents commonly used in the art.

As used herein, “fragrance composition” means any composition comprisingat least one compound of formula (I) and a base material, e.g. a diluentconventionally used in conjunction with odorants, such asdipropyleneglycol (DPG), isopropylmyristate (IPM), triethylcitrate (TEC)and alcohol (e.g. ethanol).

The following list comprises examples of known odorant molecules, whichmay be combined with the compounds of the present invention:

-   -   essential oils and extracts, e.g. tree moss absolute, basil oil,        fruit oils such as bergamot oil and mandarine oil, myrtle oil,        palmarose oil, patchouli oil, petitgrain oil, jasmine oil, rose        oil, sandalwood oil, wormwood oil, lavender oil or ylang-ylang        oil;    -   alcohols, e.g. cinnamic alcohol, cis-3-hexenol, citronellol,        Ebanol™, eugenol, farnesol, geraniol, Super Muguet™, linalool,        menthol, nerol, phenylethyl alcohol, rhodinol, Sandalore™,        terpineol or Timberol™;    -   aldehydes and ketones, e.g. anisaldehyde, α-amylcinnamaldehyde,        Georgywood™ hydroxycitronellal, Iso E® Super, Isoraldeine®,        Hedione®, Lilial®, maltol, Methyl cedryl ketone, methylionone,        verbenone or vanillin;    -   ethers and acetals, e.g. Ambrox™, geranyl methyl ether, rose        oxide or Spirambrene™;    -   esters and lactones, e.g. benzyl acetate, Cedryl acetate,        γ-decalactone, Helvetolide®, γ-undecalactone or Vetivenyl        acetate;    -   macrocycles, e.g. Ambrettolide, Ethylene brassylate or        Exaltolide®;    -   heterocycles, e.g. isobutylquinoline.

The compounds according to formula (I) may be used in a broad range offragrance applications, e.g. in any field of fine and functionalperfumery, such as perfumes, air care products, household products,laundry products, body care products and cosmetics. Further examples offine perfumery are Eau de perfume, Eau de Toilette, Eau de Cologne andSplash Cologne. Fine perfumery products are commonly based on analcoholic solution as diluent. However fine perfumery products using anoil or wax as diluent may also be included within the meaning of thisinvention. The compounds can be employed in widely varying amounts,depending upon the specific application and on the nature and quantityof other odourant ingredients. The proportion is typically from 0.0001to 10 weight percent of the application. In one embodiment, compounds ofthe present invention may be employed in a fabric softener in an amountof from 0.0001 to 0.04 weight percent. In another embodiment, compoundsof the present invention may be used in fine perfumery in amounts offrom 0.01 to 10 weight percent, more preferably between 0.01 and 5weight percent, e.g. up to 2 weight percent. However, these values aregiven only by way of example, since the experienced perfumer may alsoachieve effects or may create novel accords with lower or higherconcentrations.

The compounds as described hereinabove may be employed in a consumerproduct base simply by directly mixing the compound of formula (I), amixture thereof, or a fragrance composition with the consumer productbase, or they may, in an earlier step, be entrapped with an entrapmentmaterial, for example, polymers, capsules, microcapsules andnanocapsules, liposomes, film formers, absorbents such as carbon orzeolites, cyclic oligosaccharides and mixtures thereof, or they may bechemically bonded to substrates, which are adapted to release thefragrance molecule upon application of an external stimulus such aslight, enzyme, or the like, and then mixed with the consumer productbase.

Thus, the invention additionally provides a method of manufacturing afragrance application, comprising the incorporation of a compound offormula (I), as a fragrance ingredient, either by directly admixing thecompound to the consumer product base or by admixing a fragrancecomposition comprising a compound of formula (I), which may then bemixed with a consumer product base, using conventional techniques andmethods. Through the addition of an olfactory acceptable amount of acompound of the present invention as hereinabove described, or a mixturethereof, the odour notes of a consumer product base will be improved,enhanced or modified.

Thus, the invention furthermore provides a method for improving,enhancing or modifying a consumer product base by means of the additionthereto of an olfactorily acceptable amount of a compound of formula(I), or a mixture thereof.

The invention also provides a fragrance application comprising:

-   -   a) as odorant a compound of formula (I), or a mixture thereof;        and    -   b) a consumer product base; and    -   c) optionally a further odorant molecule.

As used herein, “consumer product base” means a composition for use as aconsumer product to fulfill specific actions, such as cleaning,softening, and caring or the like. Examples of such products includefine perfumery, e.g. perfume and eau de toilette; fabric care, householdproducts and personal care products such as laundry care detergents,rinse conditioner, personal cleansing composition, detergent fordishwasher, surface cleaner; laundry products, e.g. softener, bleach,detergent; body care products, e.g. shampoo, shower gel; air careproducts and cosmetics, e.g. deodorant, vanishing creme. This list ofproducts is given by way of illustration and is not to be regarded asbeing in any way limiting.

The compounds of formula (I) may be prepared from the correspondingaldehydes by oxidation methods known to the person skilled in the art oforganic synthesis.

The invention is now further described with reference to the followingnon-limiting examples. These examples are for the purpose ofillustration only and it is understood that variations and modificationscan be made by one skilled in the art.

The reported NMR spectra were measured in CDCl₃ if not otherwise stated;chemical shifts (δ) are reported in ppm downfield from TMS; couplingconstants J in Hz.

Flash chromatography: Merck silica gel 60 (230-400 mesh).

EXAMPLE 1: 2-METHYLUNDECANOIC ACID

Jones reagent (61 ml, containing 163 mmol CrO₃ and 280 mmol H₂SO₄) wasadded dropwise to the cooled (−25° C.) solution of 2-methylundecanal(45.0 g, 245 mmol) in acetone (80 ml) during 20 min. The solution wasstirred at −5° C. for further 15 min, then poured into a biphasicmixture of 10% aq. NaOH-solution (400 g) and toluene (400 ml) andthoroughly stirred for 15 min. The phases were separated in a separatoryfunnel (emulsions were broken by the addition of small amounts of EtOHand solid NaCl). The alkaline aqueous layer was transferred into anErlenmeyer flask, mixed with toluene (ca. 100 ml), and acidified by theaddition of 6 N aqueous HCl-solution (200 ml, 1.2 mol). The aqueouslayer is then extracted with toluene, washed neutral with half-saturatedaq. NaCl-solution and dried over MgSO₄. After removal of the solvent,the crude was subjected to a short-path distillation at 0.05mbar/111-123° C., followed by fine distillation over a Vigreux-column at0.05 mbar/118-121° C. to yield 20.1 g (41%) of 2-methylundecanoic acidas a colourless oil.

IR (thin film): 2923m, 2854m, 1703vs, 1465w, 1236w, 938w.

¹H-NMR (400 MHz, CDCl₃): 11.76 (br. s, 1H); 2.44 (hex, J=7.0 Hz, 1H);1.71-1.63 (m, 1H); 1.46-1.37 (m, 1H); 1.35-1.23 (m, 14H); 1.16 (d, J=6.8Hz, 3H); 0.87 (t, J=7.0 Hz, 3H).

¹³C-NMR (100 MHz, CDCl₃): 183.7 (s), 39.4 (d), 33.5 (t), 31.9 (t), 29.6(t), 29.5 (t), 29.5 (t), 29.3 (t), 27.1 (t), 22.7 (t), 16.8 (q), 14.1(q).

MS (EI, 70 eV): 200 (2, M+), 185 (<1), 171 (1), 157 (5), 143 (11), 129(7), 87 (41), 74 (100).

Odour description: olibanum, elemi, citrus

EXAMPLE 2: 2-METHYLDECANOIC ACID

Following the protocol according to Example 1,2-methyldecanoic acid wasprepared starting from 2-methyldecanal. The title compound was purifiedby fine distillation over a Vigreux-column at 0.05 mbar/115-130° C.(colourless oil, yield 49%).

IR (thin film): 2924m, 2855m, 1703vs, 1465w, 1238w, 938w.

¹H-NMR (400 MHz, CDCl₃): 11.59 (br. s, 1H); 2.44 (hex, J=6.9 Hz, 1H);1.73-1.62 (m, 1H); 1.47-1.37 (m, 1H); 1.36-1.22 (m, 12H); 1.16 (d, J=6.8Hz, 3H); 0.87 (t, J=7.0 Hz, 3H).

¹³C-NMR (100 MHz, CDCl₃): 183.5 (s), 39.4 (d), 33.5 (t), 31.9 (t), 29.5(t), 29.4 (t), 29.2 (t), 27.1 (t), 22.7 (t), 16.8 (q), 14.1 (q).

MS (EI, 70 eV): 186 (2, M⁺), 143 (9), 129 (11), 87 (39), 74 (100), 55(20).

Odour description: citrus, aldehydic, resinous, Olibanum.

EXAMPLE 3: 2-METHYL DODECANOIC ACID

Following the protocol according to Example 1,2-methyldodecanoic acidmay be prepared starting from 2-methyldodecanal.

Odour description: aldehydic, resinous, raspberry.

EXAMPLE 4: FURTHER COMPOUNDS

The following compounds may be prepared following the protocol accordingto Example 1: 2-ethyl decanoic acid; 2-ethyl undecanoic acid; 2-methylundec-9-enoic acid; and 2-methyl undec-10-enoic acid;

EXAMPLE 5: 2-METHYL UNDEC-9-ENOIC ACID AND 2-METHYL UNDEC-10-ENOIC ACID

a) Sulfuric acid (62%, 88.7 g, 0.56 mol, 1.1 equiv.) is added at 10° C.to diethylamine (81.4 g, 1.1 mol, 1.1 equiv.) Formaldehyde (36.5% inwater, 93.3 g, 1.12 mol, 1.12 equiv.) is added to the white suspensionat 15° C. At the same temperature are added dropwise over 25 min thesolution of BHT (0.67 g) in aldehyde iso C11 (mixture ofE-IZ-9-undecenal and 10-undecenal; 168 g, 1 mol). The mixture wasfurther stirred during 1.5 h at room temperature, during 3.5 h at 110°C. and during 16 h at room temperature. The mixture was diluted withcyclohexane and the organic layer washed 3 times with water, once withsat. aq. NaHCO₃ and twice with brine. The crude obtained after dryingthe organic layer with MgSO₄ and removing the solvents was pre-purifiedby a short-path distillation at 0.06 mbar/90° C. to isolate 119 g (66%)of a colourless oil, which was fine-distilled at 0.05 mbar/71-79° C. toisolate 104 g (58%) of a mixture of 2-methylene undec-9-enal (1) and2-methylene undec-10-enal (2) as a colourless oil.

¹H-NMR (400 MHz, CDCl₃): 9.54 (s, 1H), 6.24 (s, 1H), 5.98 (s, 1H),5.85-5.75 (m, 0.14H), 5.43-5.31 (m, 1.6H), 4.99-4.88 (m, 0.29H), 2.23(t, J=7.6, 2H), 2.03-1.90 (m, 2H), 1.62-1.56 (m, 2H), 1.45-1.39 (m, 3H),1.35-1.23 (m, 8H).

MS (EI, 70 eV): (1) 180 (M⁺, 2), 165 (2), 151 (8), 123 (9), 109 (17), 95(29), 81 (33), 67 (41), 55 (100).

b) The mixture of 2-methylene undec-9-enal (1) and 2-methyleneundec-10-enal (2) (18 g, 100 mmol) prepared above was treated withtriethylsilane (12.2 g, 105 mmol, 1.05 equiv.) andtris(triphenylphosphine)chlororhodium(I) (100 mg, 0.1 mmol, 0.1 mol-%)and the resulting solution stirred at 50° C. for 1 h and at 60° C. for 2h. The dark mixture was diluted with hexane and the solution washed 3times with water. After drying the organic layer over MgSO₄ and removalof the solvent a yellow oil was obtained (30.1 g), which was distilledat 0.06 mbar/105-133° C. to yield a colourless oil (20.8 g, 70%).

This product (15 g, 50.6 mmol) was dissolved in toluene (50 ml). Thesolution was cooled to 5° C. and a solution of tetrabutyl ammoniumfluoride (1 M in THF, 20 ml, 20 mmol, 0.4 equiv.) was added dropwiseover 4 min, followed by the addition of solid potassium fluoride (5.8 g,100 mmol, 2 equiv) and methanol (50 ml). The resulting white suspensionwas stirred at 0-5° C. for 3 h, then treated with sat. aq. NaHCO₃solution (80 ml) and stirred thoroughly for 15 min. The mixture wasextracted with methyl t-butyl ether and the organic layer washed 3 timeswith brine/water 1:1. The organic layer was dried over MgSO₄ and thesolvent removed. The resulting colourless oil (15 g) was purified byflash column chromatography over silica gel with hexane/toluene 1:1 toyield 5.74 g (31%) of a colourless oil, which was further purified bydistillation at 0.05 mbar/58-62° C. to yield 2.2 g (7%) of a colourlessoil. Of this product, 1.09 g (6 mmol) were dissolved in ethanol (20 ml)and a solution of silver nitrate (2.24 g, 13.2 mmol, 2.2 equiv.) inwater (10 ml) was added, followed by a 12.5% wt/wt aqueous sodiumhydroxide solution (30 g, 94 mmol). During the addition, the temperaturerose to 35° C. The grey emulsion was stirred intensely for 22 h at roomtemperature. The precipitate was removed by filtration and the filtercake was rinsed thoroughly with ethanol. The ethanol was removed fromthe filtrate and the residual alkaline aqueous solution was diluted withmethyl t-butyl ether. The aqueous phase was separated and the organiclayer was extracted with 4 N aq. NaOH. The combined alkaline aqueouslayers were washed with methyl t-butyl ether, then acidified with dilutehydrochloric acid to pH 1 and extracted with methyl t-butyl ether. Theorganic layer was washed with brine, dried over MgSO₄ and concentratedin the rotary evaporator. The residue was purified by bulb-to-bulbdistillation at 0.06 mbar/140-150° C. to isolate 1.15 g (96%) ofcolourless oil, which consisted of a mixture of E-2-methylundec-9-enoicacid (3a, 56.3%), Z-2-methylundec-9-enoic acid (3b, 32.4%) and2-methylundec-10-enoic acid (4, 11.3%).

IR (thin film): 3500-2600 br, 2925 m, 2855 w, 1703 vs.

¹H-NMR (400 MHz, CDCl₃): δ ppm 11.8 (br. s, 1H), 5.80 (m, 0.2H), 5.39(m, 1.8H), 4.94 (m, 0.4H), 2.44 (td, J=13.8, 6.9 Hz, 1H), 1.99 (m, 2H),1.64 (m, 3H), 1.36 (m, 10H), 1.16 (d, J=6.7 Hz, 3H).

MS (EI, 70 eV): (3a) 198 (M⁺, 4), 180 (5), 165 (<1), 125 (11), 87 (32),74 (89), 69 (65), 55 (100).

(3b) 198 (M+, 4), 180 (7), 165 (<1), 125 (13), 87 (30), 74 (91), 55(100).

(4) 198 (M+, 2), 180 (5), 165 (<1), 125 (9), 87 (24), 74 (100).

Odour description: incense, olibanum.

EXAMPLE 6: FURTHER COMPOUNDS

The following compounds may be prepared following the protocol accordingto Example 5: 2-methyl undec-8-enoic acid and 2-methyl undec-7-enoicacid.

EXAMPLE 7: PREPARATION OF PERFUME ACCORDS

Base Accord:

Ingredients Weight parts Cashmeran 10% in Diethylphtalate 8(6,7-dihydro-1,1,2,3,3-pentamethyl-4(5H)-indanone) Frankincense 50% inDiisopropylphtalate 8 Ethyl Vanillin 0.1% in Dipropylene glycol 1Georgywood* 10 (1-(1,2,3,4,5,6,7,8-octahydro-1,2,8,8-tetramethyl-2-naphthalenyl)ethanone) Hedione (methyl(2-pentyl-3-oxocyclopentyl)acetate) 20 Javanol* 10% in dipropyleneglycol 8 ((1-methyl-2-((1,2,2-trimethylbicyclo[3.1.0]hexan-3-yl)methyl)cyclopropyl)methanol) Phenoxanol(3-methyl-5-phenylpentan-1-ol) 16 Moxalone* 50% in triethyl citrate 9(1a,2,3,4,5,6,7a-octahydro-1a,3,3,4,6,6-hexamethyl-naphth[2,3-b]oxirene) Pepperwood* (dimethylcarbamic acid3,7-dimethylocta- 16 1,6-dien-3-yl ester) Dipropylene glycol 4 Total:100 *Givaudan Schweiz AG, Vernier

5.1: The replacement of 4% of dipropylene glycol in the above baseaccord formula by 4% of 2-methyldecanoic acid at 10% in dipropyleneglycol brings a fresh, sparkling, natural, citrus note and a richnatural woody piney note, characteristic of fir.

5.2: The replacement of 4% of dipropylene glycol in the above baseaccord formula by 2-methylundecanoic acid at 10% in dipropylene glycolimparts an intense, rich and natural olibanum note, characteristic ofburning olibanum.

The invention claimed is:
 1. A fragrance application comprising asodorant a compound of formula (I) or a mixture thereof,

wherein X is selected from methyl and ethyl; R is selected from C₄-C₆alkyl and C₄-C₆ alkenyl, and a consumer product base, wherein theconsumer product base is selected from the group consisting of fabriccare, detergent for dishwasher, surface cleaner, laundry products,shampoo, shower gel, cosmetics and air care products, and wherein thefragrance application comprises an olfactory acceptable amount from0.0001 to 0.01 weight % of the compound of formula (I) or a mixturethereof, wherein the compound of formula (I) or a mixture thereof isadded to improve, enhance or modify odour notes of the consumer productbase.
 2. The fragrance application according to claim 1, wherein thecompound of formula (I) is selected from the group consisting of2-methyl decanoic acid, 2-methyl undecanoic acid, 2-ethyl decanoic acid,2-ethyl undecanoic acid, 2-methyl undec-9-enoic acid, 2-methylundec-10-enoic acid, 2-methyl undec-8-enoic acid, 2-methyl undec-7-enoicacid and 2-methyl dodecanoic acid.
 3. The fragrance applicationaccording to claim 1, wherein the compound of formula (I) comprises2-methyl undecanoic acid.
 4. A method of improving, enhancing ormodifying a consumer product base comprising adding to the consumerproduct base as odorant an olfactory acceptable amount of a compound offormula (I) or a mixture thereof

wherein X is selected from methyl and ethyl; R is selected from C₄-C₆alkyl and C₄-C₆ alkenyl, wherein the olfactory acceptable amountcomprises from 0.0001 to 0.01 weight % of the compound of formula (I) ora mixture thereof and wherein the consumer product base is selected fromthe group consisting of fabric care, detergent for dishwasher, surfacecleaner, laundry products, shampoo, shower gel, cosmetics and air careproducts, wherein the compound of formula (I) or a mixture thereof isadded to improve, enhance or modify odour notes of the consumer productbase.
 5. The method according to claim 4, wherein the compound offormula (I) is selected from the group consisting of 2-methyl decanoicacid, 2-methyl undecanoic acid, 2-ethyl decanoic acid, 2-ethylundecanoic acid, 2-methyl undec-9-enoic acid, 2-methyl undec-10-enoicacid, 2-methyl undec-8-enoic acid, 2-methyl undec-7-enoic acid and2-methyl dodecanoic acid.
 6. The method according to claim 4, whereinthe compound of formula (I) comprises 2-methyl undecanoic acid.